Culture

Grief can cause inflammation that can kill, according to new research from Rice University.

The study, "Grief, Depressive Symptoms and Inflammation in the Spousally Bereaved," will appear in an upcoming edition of Psychoneuroendocrinology. It examines the impact grief has on human health. It builds on previous research from the lab of Chris Fagundes, an assistant professor of psychological sciences at Rice University and the study's lead author, who studied risk factors for inflammation.

Rice researchers conducted interviews and examined the blood of 99 people who spouses had recently died. They compared people who showed symptoms of elevated grief - such as pining for the deceased, difficulty moving on, a sense that life is meaningless and inability to accept the reality of the loss - to those who did not exhibit those behaviors. The researchers discovered that widows and widowers with elevated grief symptoms suffered up to 17 percent higher levels of bodily inflammation. And people in the top one-third of that group had a 53.4 percent higher level of inflammation than the bottom one-third of the group who did exhibit those symptoms.

"Previous research has shown that inflammation contributes to almost every disease in older adulthood," Fagundes said. "We also know that depression is linked to higher levels of inflammation, and those who lose a spouse are at considerably higher risk of major depression, heart attack, stroke and premature mortality. However, this is the first study to confirm that grief -- regardless of people's levels of depressive symptoms -- can promote inflammation, which in turn can cause negative health outcomes."

This finding is an important revelation in the study of how human behaviors and activities impact inflammation levels in the body, Fagundes said, and it adds to a growing body of work about how bereavement can affect health. His initial work showed why those who have been widowed are at higher risk of cardiovascular problems, bodily symptoms and premature mortality by comparing inflammation in spousally bereaved individuals to matched controls.

"This work shows who, among those who are bereaved, are at highest risk," Fagundes said. "Now that we know these two key findings, we can design interventions to target this risk factor in those who are most at risk through behavioral or pharmacological approaches."

The study was co-authored by Rice psychological sciences graduate students Ryan Brown and Michelle Chen; Kyle Murdock, an assistant professor of biobehavioral health at Pennsylvania State University and a former postdoctoral research fellow in the Fagundes laboratory at Rice; Levi Saucedo, a research assistant at Rice; Angie LeRoy, a postdoctoral research fellow at Rice; Lydia Wu, a fellow in psychological sciences at Rice; Luz Garcini, a postdoctoral research fellow at Rice; Anoushka Shahane, a Ph.D. student at Rice; Faiza Baameur, a postdoctoral fellow of pharmacology at Vanderbilt University; and Cobi Heijnen, a researcher at MD Anderson Cancer Center in Houston.

This work was supported by the National Heart, Lung and Blood Institute. To obtain a copy of the study, contact David Ruth, director of national media relations at Rice, at 713-348-6327 or david@rice.edu.

People who need to make a good impression on dates or in job interviews should concentrate on communicating the hard work and effort behind their success, rather than just emphasising their talent, new research from Cass Business School has found.

In Impression (Mis) Management When Communicating Success, published in Basic and Applied Social Psychology, Dr Janina Steinmetz investigated how people attribute their success on dates and job interviews, and whether these attributions were successful with their audiences.

She found - contrary to what many of us think - that success alone may not be enough to make a positive impression. Instead, she suggests that people should ensure they talk about the struggle behind their story to appear more likeable.

Dr Steinmetz conducted three experiments with participants from the United States and the Netherlands, with people from all age ranges (18-75) and with an even gender balance between male and female. Two of the experiments emulated job interviews (using working adults) and one emulated a date (using students). Participants were asked to imagine themselves in the role of the impression manager (interviewee or 'sharer' on a date) or the receiver (interviewer or 'listener' on a date).

The 'impression manager' was asked to speak about themselves in in a positive way and feedback was given by the receiver detailing what they wanted to hear more about - the talent and success, or the hard work and effort behind it.

All three experiments found the impression managers overemphasised their talents and successes and did not share the effort and hard work behind them - something that the receivers wanted to hear about.

Dr Steinmetz said it was clear that communicating success and talent in job interviews or on dates is important but it is just as important to tell the story of the hard work and effort behind it to create a warmer, positive, more relatable first impression.

"A success story isn't complete without the hard work and explanation of why we were successful. Did the success come easy, thanks to one's talents, or was it attained through hard work? Both of these attributions can be part of successful self-promotion, but my research shows that emphasising effort is more likely to garner a positive impression and people really want to know the story behind your success.

"For example, if you're on a date and talking about a marathon that you recently ran, perhaps talk about all the training that helped you to cross the finish line. Or, if you're in a job interview and are talking about a successful project that you led to completion, include a few details about the challenges along the way, and how you overcame them."

When it comes to preventing blood clots after a knee replacement, good old aspirin may be just as effective as newer, more expensive drugs.

That swap could help reduce the cost of caring for the nearly 1 million Americans who have a knee fixed each year, Michigan Medicine researchers say.

After knee surgery, there's a risk of blood clots in the legs or lungs. So it's routine for patients to take clot-preventing drugs for some time afterward.

Some doctors choose powerful anti-clotting drugs like heparin (Lovenox) and rivaroxaban (Xarelto), but it hasn't been clear whether these expensive prescription drugs work any better than cheap, readily available aspirin.

"Aspirin alone may provide similar protection compared to anticoagulation treatments," says Brian R. Hallstrom, M.D., an orthopaedic surgeon and associate chair for quality and safety at the University of Michigan Department of Orthopaedic Surgery.

Hallstrom is the lead author of a new study published in JAMA Surgery that found few patients developed a blood clot after surgery, and those patients on aspirin fared just as well as those on anticoagulants.

Aspirin use growing

During the two-year study period from 2013 to 2015, aspirin use rose from 10 percent to 50 percent among the patients cared for by orthopaedic surgeons in the Michigan Arthroplasty Registry Collaborative Quality Initiative, a statewide effort to give patients the best possible recovery and outcomes after hip and knee replacements.

Since then, the shift has become even more distinct: Aspirin prescribing has risen to 70 percent among Michigan surgeons, says Hallstrom, who is co-director of the initiative and a health services researcher at U-M's Institute for Healthcare Policy and Innovation.

Based on the experience of 41,537 Michigan patients undergoing knee replacement, the study may further the debate about the routine use of aspirin for clot prevention.

A recent Canadian study looked at the issue, but the analysis had a caveat: Each of the more than 3,400 clinical trial patients received rivaroxaban the first five days after surgery. After that, they continued with the drug or switched to aspirin.

The new U-M study suggests patients may be adequately protected if they take aspirin alone from day one.

"This study is truly a real-world experience of what happened in Michigan when the majority of surgeons switched to aspirin," Hallstrom says. "The incidence of blood clots, pulmonary embolus and death did not increase despite this dramatic change in practice."

Shifting procedure and dialogue

Over the past decade, surgeons have turned away from powerful anticoagulants and toward aspirin used in addition to nondrug improvements such as compression devices for thwarting clots.

These days, most patients have a generally low risk of blood clots after knee replacement for a number of reasons. Those reasons include shorter surgical times, less invasive procedures and use of regional anesthesia that allows early mobilization after surgery, Hallstrom says. Some patients are even going home the same day.

"The most important way to prevent blood clots is getting moving," says Hallstrom, noting that people are at risk for blood clots when they sit or lie in one position for too long, such as on an airplane or a hospital bed.

Still, pharmaceutical recommendations vary.

The critical care specialists who make up the American College of Chest Physicians favor heparin to reduce the risk of blood clots, while the American Academy of Orthopaedic Surgeons guidelines state that no one drug is better than another for preventing clots.

Advantages of aspirin

The U-M study involved patients undergoing knee replacement surgery at any of the 29 Michigan hospitals in the surgical quality group. One-third of the patients took aspirin alone; 54 percent took only an anticoagulant; and 13 percent took an aspirin/anticoagulant combination.

Over three months, just 1.16 percent of aspirin patients developed a serious blood clot. That was true for 1.42 percent of anticoagulant patients, according to the Michigan study. This was not statistically different.

So, neither drug appeared better than the other -- but aspirin has some obvious advantages.

"Aspirin is easy to take and much less expensive," Hallstrom says. "Patients can get it over the counter for pennies, while the other anticoagulants require monitoring, injections, frequent dose adjustments and are extremely expensive."

The reported cost for a 30-day supply of rivaroxaban is approximately $379 to $450; heparin is estimated at $450 to $890. Although warfarin costs a few dollars for a 30-day supply, its cost approaches that of the other anticoagulants when doctor visits for monitoring are factored in, Hallstrom says.

In contrast, aspirin costs approximately $2 a month.

The study suggests most patients can have just aspirin without increasing the risk for venous thromboembolism, but doctors need to consider factors such as a patient's history of clots, obesity and ability to mobilize after surgery when determining the best measure for clot prevention, Hallstrom adds.

(Vienna, October 23, 2018) Oesophageal microbiota may help to improve the diagnosis and management of oesophageal cancer, according to the results of a study presented today. Researchers from Italy directed by Professor Cammarota have found a unique pattern of microbes living in the oesophagus of people with oesophageal cancer or Barrett's oesophagus, which could potentially be used to identify at-risk individuals and pave the way for new types of treatment in the future.

Speaking at UEG Week 2018 in Vienna, Austria, lead researcher, Dr Loris Riccardo Lopetuso from the Catholic University of Rome, Italy, said: "Despite the introduction of novel therapies such as surgery, chemotherapy, and radiotherapy, the prognosis for people with oesophageal cancer remains poor. We need to develop a better understanding of what causes normal oesophageal cells to become malignant so we can find at-risk individuals as early as possible and develop alternative therapeutic strategies."

Oesophageal cancer is the 8th most common cancer worldwide and the 6th most common cause of cancer-related death. Most people present with established disease, so rates of mortality are high in most countries. Known risk factors include gastroesophageal reflux disease (GORD), obesity, smoking, low fruit/vegetable intake, and alcohol consumption, but other factors, including upper digestive tract microbiota are thought to be involved.

In the study presented today, researchers aimed to characterize the composition of the oesophageal microbiota in patients with oesophageal cancer compared with patients with Barrett's oesophagus and a control group of people with no evidence of the disease. Biopsy samples from six newly-diagnosed patients with oesophageal cancer, 10 with Barrett's oesophagus and 10 controls were analysed for microbiota composition.

A higher level of bacterial diversity was reported for patients with oesophageal cancer compared with the controls; there was a relative abundance of Bacteroidetes and a relative paucity of Firmicutes (different categories of microbiota) in the patients with oesophageal cancer compared with the controls. There were also lower levels of Streptococcus, and higher levels of Veillonella, Porphyromonas, and Prevotella (different types of bacteria) in those with oesophageal cancer compared with Barrett's oesophagus patients and the controls.

"These results indicate that there is a unique microbial signature for oesophageal cancer that might represent a risk factor for this condition," said Dr Lopetuso. "If these findings are confirmed in our further analyses, it may be possible to imagine innovative diagnostic and therapeutic tools to help us manage this condition more successfully."

New research led by the University of Sydney has revealed the life expectancy of chocolate Labradors is significantly lower than their black and yellow counterparts.

The study of more than 33,000 United Kingdom-based Labrador retrievers of all colours shows chocolate Labradors also have a higher incidence of ear infections and skin disease. Its findings were published in the open access journal Canine Genetics and Epidemiology today.

Part of the University's VetCompass™ Programme, which collects and analyses electronic patient data on dogs, the research is being replicated in Australia, where Labradors are the most popular breed of dog.

In the UK, the median longevity of non-chocolate Labradors is 12.1 years, more than 10 percent longer than those with chocolate coats. The prevalence of ear inflammation (otitis externa) was twice as high in chocolate Labradors, who were four times more likely to have suffered from pyo-traumatic dermatitis (also known as hot-spot).

Lead author Professor Paul McGreevy, from the University's Faculty of Science, said the relationship between coat colour and disease came as a surprise to researchers. The UK findings may not hold in Australian Labradors, he said, but warrant investigation.

"The relationships between coat colour and disease may reflect an inadvertent consequence of breeding certain pigmentations," he said. "Because chocolate colour is recessive in dogs, the gene for this colour must be present in both parents for their puppies to be chocolate. Breeders targeting this colour may therefore be more likely to breed only Labradors carrying the chocolate coat gene. It may be that the resulting reduced gene pool includes a higher proportion of genes conducive to ear and skin conditions."

Across the entire Labrador population, the most common health conditions found were obesity, ear infections and joint conditions.

"We found that 8.8 percent of UK Labradors are overweight or obese, one of the highest percentages among dog breeds in the VetCompass™ database," Professor McGreevy said.

The prevalence was higher among male dogs who had been neutered.

Labrador retrievers under primary veterinary care in the UK was co-authored with colleagues from the London's Royal Veterinary College (RVC), where the VetCompass™ programme™ began in 2007, as a collaboration with the University of Sydney. VetCompass Australia now operates as a consortium comprising all of Australia's veterinary schools, supported by the Australian Research Council.

Computer bits are binary, with a value of 0 or 1. By contrast, neurons in the brain can have all kinds of different internal states, depending on the input that they received. This allows the brain to process information in a more energy-efficient manner than a computer. University of Groningen (UG) physicists are working on memristors, resistors with a memory, made from niobium-doped strontium titanate, which mimic how neurons work. Their results were published in the Journal of Applied Physics on 21 October.

The brain is superior to traditional computers in many ways. Brain cells use less energy, process information faster and are more adaptable. The way that brain cells respond to a stimulus depends on the information that they have received, which potentiates or inhibits the neurons. Scientists are working on new types of devices which can mimic this behavior, called memristors.

Memory

UG researcher Anouk Goossens, the first author of the paper, tested memristors made from niobium-doped strontium titanate. The conductivity of the memristors is controlled by an electric field in an analog fashion: 'We use the system's ability to switch resistance: by applying voltage pulses, we can control the resistance, and using a low voltage we read out the current in different states. The strength of the pulse determines the resistance in the device. We have shown a resistance ratio of at least 1000 to be realizable. We then measured what happened over time.' Goossens was especially interested in the time dynamics of the resistance states.

She observed that the duration of the pulse with which the resistance was set determined how long the 'memory' lasted. This could be between one to four hours for pulses lasting between a second and two minutes. Furthermore, she found that after 100 switching cycles, the material showed no signs of fatigue.

Forgetting

'There are different things you could do with this', says Goossens. 'By "teaching" the device in different ways, using different pulses, we can change its behavior.' The fact that the resistance changes over time can also be useful: 'These systems can forget, just like the brain. It allows me to use time as a variable parameter.' In addition, the devices that Goossens made combine both memory and processing in one device, which is more efficient than traditional computer architecture in which storage (on magnetic hard discs) and processing (in the CPU) are separated.

Goossens conducted the experiments described in the paper during a research project as part of the Master in Nanoscience degree programme at the University of Groningen. Goossens' research project took place within the group of students supervised by Dr. Tamalika Banerjee of Spintronics of Functional Materials. She is now a Ph.D. student in the same group.

Questions

Before building brain-like circuits with her device, Goossens plans to conduct experiments to really understand what happens within the material. 'If we don't know exactly how it works, we can't solve any problems that might occur in these circuits. So, we have to understand the physical properties of the material: what does it do, and why?'

Questions that Goossens want to answer include what parameters influence the states that are achieved. 'And if we manufacture 100 of these devices, do they all work the same? If they don't, and there is device-to-device variation, that doesn't have to be a problem. After all, not all elements in the brain are the same.'

By merging the ancient art of origami with 21st century technology, researchers have created a one-step approach to fabricating complex origami structures whose light weight, expandability, and strength could have applications in everything from biomedical devices to equipment used in space exploration. Until now, making such structures has involved multiple steps, more than one material, and assembly from smaller parts.

"What we have here is the proof of concept of an integrated system for manufacturing complex origami. It has tremendous potential applications," said Glaucio H. Paulino, a professor at the School of Civil and Environmental Engineering at the Georgia Institute of Technology and a leader in the growing field of origami engineering, or using the principles of origami, mathematics and geometry to make useful things. Last fall Georgia Tech became the first university in the country to offer a course on origami engineering, which Paulino taught.

The researchers used a relatively new kind of 3D printing called Digital Light Processing (DLP) to create groundbreaking origami structures that are not only capable of holding significant weight but can also be folded and refolded repeatedly in an action similar to the slow push and pull of an accordion. When Paulino first reported these structures, or "zippered tubes," in 2015, they were made of paper and required gluing. In the current work, the zippered tubes - and complex structures made out of them - are composed of one plastic (a polymer) and do not require assembly.

The work was reported in a recent issue of Soft Matter, a journal published by the Royal Society of Chemistry. The primary authors are Paulino; H. Jerry Qi, a professor in Georgia Tech's George W. Woodruff School of Mechanical Engineering; and Daining Fang of Peking University and the Beijing Institute of Technology. Other authors are Zeang Zhao, a visiting student at Georgia Tech now at Peking University; Qiang Zhang of Peking University; and Xiao Kuang and Jiangtao Wu of Georgia Tech.

An Emerging Technology

There are many different types of 3D printing technologies. The most familiar, inkjet, has been around for some 20 years. But until now, it has been difficult to create 3D-printed structures with the intricate hollow features associated with complex origami because removing the supporting materials necessary to print these structures is challenging. Further, unlike paper, the 3D-printed materials could not be folded numerous times without breaking.

Enter DLP and some creative engineering. According to Qi, a leader in the emerging field collaborating with Fang's group at Peking University, DLP has been in the lab for a while, but commercialization only began about five years ago. Unlike other 3D printing techniques, it creates structures by printing successive layers of a liquid resin that is then cured, or hardened, by ultraviolet light.

For the current work, the researchers first developed a new resin that, when cured, is very strong. "We wanted a material that is not only soft, but can also be folded hundreds of times without breaking," said Qi. The resin, in turn, is key to an equally important element of the work: tiny hinges. These hinges, which occur along the creases where the origami structure folds, allow folding because they are made of a thinner layer of resin than the larger panels of which they are part. (The panels make up the bulk of the structure.)

Together the new resin and hinges worked. The team used DLP to create several origami structures ranging from the individual origami cells that the zippered tubes are composed of to a complex bridge composed of many zippered tubes. All were subjected to tests that showed they were not only capable of carrying about 100 times the weight of the origami structure, but also could be repeatedly folded and unfolded without breaking. "I have a piece that I printed about six months ago that I demonstrate for people all the time, and it's still fine," said Qi.

What's Next?

What's next? Among other things, Qi is working to make the printing even easier while also exploring ways to print materials with different properties. Meanwhile, Paulino's team recently created a new origami pattern on the computer that he is excited about but that he has been unable to physically make because it is so complex. "I think the new system could bring it to life," he said.

Munich, Germany, 20 October 2018 - Immunotherapy improves survival in some patients with metastatic triple negative breast cancer, according to late-breaking results from the IMpassion130 trial reported at the ESMO 2018 Congress in Munich. (1)

Prof. Peter Schmid, first author, said the results "will change the way triple-negative breast cancer is treated". "Atezolizumab in combination with nab-paclitaxel is the first targeted treatment to improve survival in metastatic triple negative breast cancer," said Schmid, Clinical Director of London's St. Bartholomew's Breast Cancer Centre, Barts Health NHS Trust, UK and lead of the Centre for Experimental Cancer Medicine, Barts Cancer Institute, Queen Mary University of London, UK. "It is also the first immune therapy to improve outcome in this cancer. Most of the survival benefit was in patients with PD-L1 positive tumours."

Triple negative breast cancer is the most aggressive type of breast cancer. It is relatively rare and often affects younger women. Once the disease becomes metastatic, the median survival is around 12 to 15 months. Triple negative breast cancer does not have receptors for the hormones oestrogen or the protein HER2, meaning it cannot be treated with hormone therapy or drugs targeting HER2. The main drug treatment is chemotherapy and most patients develop resistance to chemotherapy within a few months.

The phase III IMpassion 130 trial enrolled 902 patients with metastatic triple negative breast cancer who had not received prior treatment for metastatic disease. Patients were randomly allocated to standard chemotherapy (nab-paclitaxel) plus atezolizumab, an antibody targeting the protein PD-L1, or to standard chemotherapy plus placebo. The two main objectives were to see whether the drug combination could slow cancer growth (progression-free survival) and prolong life (overall survival) in all patients and in those expressing PD-L1. The median follow-up was 12.9 months.

The combination therapy reduced the risk of disease worsening or death by 20% in all patients and 38% in the subgroup expressing PD-L1. In the entire study population, the median progression free survival was 7.2 months with the combination and 5.5 months with chemotherapy alone, with a hazard ratio (HR) of 0.80 (p=0.0025). In the PD-L1 positive group, the median progression free survival was 7.5 months with the combination and 5.0 months with chemotherapy alone (HR 0.62, p

More than half of patients were alive at the time of analysis, so this was an interim assessment of overall survival. In patients with PD-L1 positive tumours, the median overall survival was 25.0 months with the combination compared to 15.5 months with standard chemotherapy alone (HR 0.62). In all patients, survival was 21.3 months with the combination versus 17.6 months with chemotherapy alone which was not statistically different, likely because of the short follow-up.

The proportion of patients responding to treatment (objective response rate) was higher with the combination compared to chemotherapy alone for all patients (56% versus 46%) and those with PD-L1 positive tumours (59% versus 43%).

Schmid said the combination therapy was well tolerated. Most side effects were due to chemotherapy and occurred at a similar rate in both treatment groups, although there was a minor increase in nausea and cough in the combination group. Side effects related to immune therapy were rare, the most common being hypothyroidism which occurred in 17.3% of patients receiving the drug combination and 4.3% receiving chemotherapy alone.

Schmid said: "Immune therapy on top of standard chemotherapy prolonged survival by ten months in patients with tumours expressing PD-L1. This combination should become a new treatment option for patients with metastatic triple negative breast cancer."

Commenting on the results for ESMO, Dr Marleen Kok, Medical Oncologist, The Netherlands Cancer Institute, Amsterdam, said: "This is the first randomised phase III trial providing evidence that adding immune therapy to standard chemotherapy increases progression-free survival in metastatic triple negative breast cancer, particularly in patients with PD-L1 positive tumours, and extends overall survival in the PD-L1 positive subgroup. While the benefit in terms of progression-free survival was relatively small, around three months, the gain in overall survival in the PD-L1 positive subgroup was impressive with a ten-month benefit. Around 40% of the tumours were PD-L1 positive. The IMpassion 130 data will probably change the treatment landscape for our metastatic triple negative breast cancer patients."

Kok noted that it is still not clear what the best chemotherapy backbone is for anti-PD-(L)1 treatment and that many trials are ongoing, evaluating the additional effect of anti-PD-(L)1 on top of chemotherapy in metastatic breast cancer but also for early breast cancer patients. "This should help answer the question of which chemotherapy backbone is most effective in combination with anti-PD-(L)1." she said. "We also need more studies to determine a biomarker for selecting patients most likely to benefit from this treatment."

SAN DIEGO, Calif. - Geneticists have assembled the largest sets of African genomic data available to date, creating a resource that will help researchers understand the genetic structure of Africa as well as the effects of genetic variation on protein function and disease. The findings underscore the importance of including globally diverse participant cohorts in genetics research, and were presented in a plenary session at the American Society of Human Genetics (ASHG) 2018 Annual Meeting in San Diego, Calif.

The researchers collected and analyzed genome-wide data from 6,400 individuals from rural Uganda, including the whole genome sequences of 1,978 people within that group. They combined this with data from an additional 7,784 individuals from other African countries, in the first genome-wide association study (GWAS) to analyze multiple traits across Africa.

"This study represents one of the largest and most comprehensive efforts to identify genetic associations with disease within African populations, and will provide a roadmap for large-scale GWAS across the region," said Ayesha Motala, MD, FRCP, a leader of the study and professor at the University of KwaZulu-Natal.

"Prior to our work, there were only a few hundred whole genome sequences available from Africa," said Deepti Gurdasani, MD, PhD, from the Wellcome Sanger Institute, who presented the research. "Most of the information we had was from African-American populations, which didn't capture the full diversity of the continent."

After compiling the data, Dr. Gurdasani and her colleagues assessed genetic similarities and differences within the cohort, identifying commonalities among those who migrated to Uganda from the same regions. They also found a complex mixture of similarities between the Ugandan genomes, ancient East African populations, and Eurasian genomes. These findings suggest that modern Ugandan genomes represent the complex history of migration in the region, and that they have been shaped by multiple mixture events over thousands of years, including mixture with genomes resembling those in modern Europe.

In addition, the researchers examined genetic influences on a variety of traits and diseases in the larger GWAS cohort, identifying 10 new associations specific to African populations. For example, they discovered an association between a deletion in the HBA1/HBA2 gene, known to cause the blood disorder alpha thalassemia, and blood bilirubin levels. This deletion is common among Africans, found in approximately 22% of individuals, but rare among previously studied Europeans.

"Although it correlates with disease, this variant has been shown to protect people from severe malaria, which presents a stronger advantage in Africa than in Europe and has enabled the variant to rise in frequency within Africa," Dr. Gurdasani explained.

The study also found an association between HBA1/HBA2 deletion and the blood's level of the protein HbA1c, high levels of which are often used to diagnose diabetes. "The high frequency of thalassemia in some African populations may affect the accuracy of this test, as it can modify HbA1c independently of glucose levels," Dr. Gurdasani said.

Beyond their own analysis, the researchers hope their data will help other scientists better understand the genetic diversity of African populations and develop cost-effective tools to capture genome variation for future studies. Future work will also include detailed mapping of the cause-and-effect relationships between genetic variants through examining functional impact of variants on gene expression.

As next steps, the researchers plan to expand their genomic data set to populations across Africa, by sampling diverse indigenous populations, and expanding the GWAS to about 75,000 individuals.

WHAT: 11th World Stroke Congress brings together leading international stroke experts and an unparalleled scientific program covering epidemiology, prevention, acute care, rehabilitation and recovery in 100s of sessions and oral posters. Congress is attended by stroke professionals, researchers, policy makers, survivors and caregivers from around the world. #worldstroke2018

WHERE: Montreal, Canada, Palais des Congrès

WHEN: October 17 - 20, 2018

MEDIA OPPORTUNTIES: Stroke experts and people with lived experience of stroke will be available for interviews.

TODAY'S CONGRESS HIGHLIGHTS

Late-breaking trials

A study of Nationwide Implementation of Mechanical Thrombectomy in Germany will be presented by Dr. Christian Weimar (8:35 am, Hall H). The study found that a wide range of both IVT and MT rates in German ischemic stroke patients indicates the need for further improvement of access to acute recanalization therapies in many, mainly rural, regions.

Dr. David Gladstone of the University of Toronto and Sunnybrook Research Institute will present the results of a study evaluating the use of the drug rivaroxaban versus acetylsalicylic acid (ASA) to prevent strokes in patients with an enlarged left atrium of the heart. The results showed some potential benefit from rivaroxaban but caution was urged. "We are seeing a very intriguing signal here, and it has biological plausibility, but it is going to require independent validation before making any changes to practice recommendations," Dr. Gladstone said. (8:53 am, Hall H)

HOT TOPIC: Review of U.S. hospital statistics shows rise in stroke incidence among marijuana users from 2010-14 while overall stroke prevalence remained stable

A five-year study of hospital statistics from the United States shows that the incidence of stroke has risen steadily among marijuana users even though the overall rate of stroke remained constant over the same period.

The study, presented today during the third day of the World Stroke Congress in Montreal, looked at U.S. hospital statistics from 2010 to 2014. It examined a total of 2.3 million hospitalizations among people who used marijuana recreationally. Of these, 32,231, or 1.4 percent, had a stroke including 19,452 with acute ischemic stroke (AIS).

Over the five years studied, the rate of stroke of all types among marijuana users increased from 1.3 percent to 1.5 percent. The rate of AIS increased from 0.7 percent to 0.9 percent. During the same five-year period, the prevalence of stroke among all patients was stable.

As result, the researchers conclude that these growing trends of stroke among marijuana users "warrant further prospective studies to evaluate the marijuana-stroke association amidst legalization of recreational use."

The researchers noted in introducing their study that marijuana "has a potential link to stroke owing to cerebrovascular effects of cannabinoids."

HOT TOPIC: Young stroke survivors at high long-term risk of adverse outcomes

A significant percentage of strokes - estimated from 8-21 per cent - affect adults under age 45. A Canadian study by senior author Dr. Richard Swartz and his team sought to determine what the future might hold for these young patients who show no early complications from their initial stroke.

This analysis of more than 26,000 young stroke survivors using data from the Institute for Clinical Evaluative Sciences (ICES) showed that, although absolute rates of adverse events including recurrent stroke, heart attack, death and institutionalization were low among young clinically stable stroke patients, these patients still showed 7 times the risk of having an adverse complication one year after their initial stroke compared to only twice the risk among older patients. After accounting for other vascular risk factors, long-term risks remained at almost 3 times that of young controls, even for these patients who were clinically stable and had no early complications during what is considered the high-risk period immediately after a stroke.

"This study shows us that even young stroke and TIA patients who are clinically stable after their stroke remain at a significant risk of adverse events, like another stroke, death or requiring long- term care," said lead study author Dr. Jodi Edwards of the Brain and Heart Nexus Research Program at the University of Ottawa Heart Institute. "This is important as it highlights the need for guidelines and strategies for long-term aggressive prevention to reduce stroke risk in
young stroke patients."

HOT TOPIC: Three studies highlight changes in stroke care in Quebec

With the World Stroke Congress being held in Montreal it is appropriate that there are three presentations concerning the evaluation of different aspects of stroke care in the province of Quebec. The lead author is Dr. Laurie Lambert, Coordinator of the Cardiovascular Evaluation Unit of Quebec's Institut national d'excellence en santé et en services sociaux (INESSS).

The first presentation evaluates changes in processes and quality of care in Québec's comprehensive stroke centres following a province-wide field evaluation in 2013-14 and the development and implementation of a plan to promote best practices by the Ministry of Health. It found that times to initiating treatment improved, with the proportion treated with thrombolysis in less than 60 minutes increasing from 47 to 80 per cent and that more patients in these centres were admitted to a stroke unit: 91 per cent in 2016-17 compared to 75 per cent previously.

The second presentation compares care pathways in the four regional networks and the third compares treatment delays for thrombectomy between direct admission and inter-hospital transfer patients. For transferred patients, median first door-to-puncture time was 171 minutes (142-224). For patients directly admitted to a comprehensive stroke centre, the median first door-to-puncture was 69 minutes (50-100).

HOT TOPIC: Canadian researchers identify age and sex differences in stroke care

Two studies by Toronto researchers look at age and sex differences in stroke care in Canada. One study looking at data from 2003-16 concluded that in-hospital deaths from stroke decreased for all patients, but the group most at risk is older women.

The second study by the same researchers was presented on Oct. 18 and looked at data from 2014-16. It concluded younger adults are more likely to get alteplase clot-busting medication, access stroke units and be discharged home independently than older adults, and women of all ages are less likely to be discharged home independently.

HOT TOPICS: Other presentations of interest on the third day of the Congress:

A Canadian study mapped stroke care facilities across Canada using geospatial software to evaluate access by distance and drive times. It concludes that most Canadians live within a 300-km drive to prevention services (95.5 per cent), endovascular therapy (79.1 per cent) and rehabilitation services (97.8 per cent); however due to Canada's geography, weather and resource challenges in more rural and remote communities, many of the eligible patients are not able to reach stroke hospitals in time to make a difference in their recovery and are left with lasting deficits from stroke.

SESSION 4 10:05-10:35

A 30-minute platform discussion in the Exhibition Hall at 10:05 am brings together world experts to discuss how to put people living with stroke and non-communicable diseases (NCDs) at the centre of healthcare. If the NCD response is to be successful, it is imperative to leave no-one behind. Patients are by definition at the very centre of healthcare, and people living with and affected by stroke and NCDs will be essential to accelerate the realization of global NCD targets. People living with NCDs, their carers, and NCD survivors must be empowered to deal with the disease in the long term. Furthermore, they need to shape the NCD response and to give an effective response against stigma and discrimination faced by people living with stroke. This applies from the level of advocacy and policy development, through to design, implementation, and evaluation of programmes. Panelists include Dr. Mayowa Owolabi, Professor of Neurology, and Dean, Faculty of Clinical Sciences, University of Ibadan (Nigeria), Jon Barrick, President, Stroke Alliance for Europe (SAFE) (UK), Stephanie Mohl, Vice President, American Stroke Association (USA) and Jennifer Monaghan, stroke survivor, Living with Stroke program (Canada). For live updates, follow @ncdallliance and #enoughNCDs

A discussion on chronic and end-of-life care for people with stroke and NCDs takes place in the Exhibition Hall at 12:40. NCDs are typically chronic conditions which require particular care towards the end of life. The WHO estimates that 40 million people are in need of palliative care each year - but that 86% do not receive it. The greatest gaps can be observed in developing country settings. Once implemented, it is imperative that end-of-life care services are holistic, extending far beyond physical treatment. The need for proper psychological and spiritual support for the person at the centre of the care, and for those around them, cannot be underestimated. Panelists include Dr. Pooja Khatri, Professor of Neurology, Director of Acute Stroke, UC Health (USA), Dr. Dylan Blacquiere, Neurologist, Saint John Regional Hospital (Canada), Dr. Gilian Mead, Professor of Stroke and Elderly Care Medicine, University of Edinburgh (UK), and Rita Melifonwu, Founder and CEO, Stroke Action Nigeria (Nigeria)

AUSTIN, Texas, Oct. 19, 2018 -- Despite a policy change to provide free abortion services for women traveling from Northern Ireland to clinics in Great Britain, Northern Irish women still experience multiple barriers to accessing care, according to new research from the LBJ School of Public Affairs at The University of Texas at Austin. The study also found that some women preferred to use medication from online telemedicine services to self-manage their abortions at home, but that the experience is dominated by fear and isolation due to the risk of prosecution.

Northern Ireland's abortion laws permit the procedure only to preserve a woman's life or prevent permanent long-term physical or mental injury. Any abortion taking place outside the law is punishable by up to life in prison.

Abigail Aiken, an assistant professor of public affairs and a fellow of the Richter Chair in Global Health Policy at the LBJ School, conducted anonymous in-depth interviews with 30 women living in Northern Ireland who either traveled to England to obtain an abortion in a clinic or who self-managed a medication abortion at home using online telemedicine. Results, which were peer-reviewed and published in BMJ Sexual and Reproductive Health, show barriers to traveling for abortion services, including the cost of travel, the inability to receive care confidentially and the challenges of arranging child care or taking time away from work.

"The recent policy change to provide free abortions for women traveling from Northern Ireland to clinics in Great Britain has not been sufficient to create a reliable and accessible pathway to care," Aiken said. "In addition to the physical toll and emotional stress of traveling overseas, many women do not have the required travel documents or need to keep their abortions secret from their families or communities."

Women in the study often said they found self-managing their abortions at home with medication more acceptable than travel. But those in the study who chose this option said they experienced severe anxiety about when or even whether they would receive the medications if Northern Irish Customs seized or delayed their packages. Some tried less effective or even unsafe methods while they waited.

Finally, the lack of clarity surrounding the duties of health care providers to report self-managed abortion led women in the study to mistrust the health care system. Although the Northern Ireland Department of Health, Social Services and Public Safety declared in 2016 that medical personnel who treat women experiencing miscarriage symptoms aren't required to ask about or report an attempted abortion, women still feel compelled to either lie to their doctors or avoid seeing a health care professional altogether.

Earlier this year, an overwhelming majority in the Republic of Ireland voted to repeal the Eighth Amendment outlawing abortion, and legislators in the Isle of Man also voted to legalize the procedure -- moves that put pressure on lawmakers in Northern Ireland and the U.K. Parliament to re-examine the country's abortion laws. In a 2017 survey, nearly 80 percent of Northern Ireland's population supported changing current regulations.

A team of researchers at Baylor College of Medicine and Texas Children's Hospital has revealed a connection between mTORC1 and Src, two proteins known to be hyperactive in cancer. The study, published in the journal Nature Communications, shows that Src is necessary and sufficient to activate mTORC1 and offers the possibility to develop novel approaches to control cancer growth.

"We started this study because we wanted to investigate whether the increased activities of both proteins Src and mTORC1 in cancer were connected," said Dr. Rituraj Pal, postdoctoral associate of molecular and human genetics and the first author of this study.

mTORC1 is essential for the survival of all cells. It is at the heart of the mechanisms that regulate cellular metabolism, growth and proliferation. mTORC1 plays a central role in maintaining the balance between the processes that break down complex molecules (catabolism) and those that build cellular molecules (anabolism). If this balance is disrupted, for instance, if catabolism supersedes anabolism or vice versa, disease may follow.

To balance cellular metabolism, mTORC1 integrates a number of signals, including those related to growth factors and amino acid availability. Signals that promote mTORC1 activation trigger cell growth by promoting protein synthesis. On the other hand, signals that inactivate mTORC1 result in the cells breaking down complex molecules to produce energy.

In this study, the researchers studied whether Src contributed to the regulation of mTORC1 that is mediated by amino acids.

"Amino acids activate mTORC1 and, when they were removed, mTORC1 activity was reduced and the downstream activity of mTORC1 also was decreased," said Dr. Marco Sardiello, assistant professor of molecular and human genetics at Baylor and a member of the Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital. "Amino acids do not act directly on mTORC1. We found that Src plays an essential role in this amino acid-mediated regulation of mTORC1 activity."

The researchers think that the connection between mTORC1 and Src is analogous to that of an AC machine and its thermostat.

"When the temperature reaches the set value, the thermostat will turn the AC on. When the temp drops below that value, the thermostat will turn the AC off," Pal said. "Src is doing something similar. When it's informed of the presence of amino acids (analogous to the temperature reaching the set value), Src is sufficient and necessary to pass on this information to the rest of the system and mTORC1 is activated. When amino acids are absent (analogous to the temperature dropping below the set value), then Src will mediate the inactivation of mTORC1."
When the researchers modified Src so it would be constantly active, it over-wrote the effect of amino acids on mTORC1, which remained active even in the absence of amino acids. When Src is hyperactive, it is like the thermostat malfunctioning, continuously signaling the system to stay on even if the temperature is below the set value and no additional cooling is necessary.
The analogy also works the other way. If the thermostat is broken, even if it's very hot, the AC won't turn on. So, if Src is defective in such a way, it won't relay the necessary information for mTORC1 to be activated, even if it's necessary for the cell to work properly.

"This role of Src was completely unknown and unexpected," Pal said. "We have discovered that Src is necessary and sufficient to activate mTORC1."

These findings have important implications for cancer studies. They imply that in those cancers in which Src is hyperactive (the thermostat is malfunctioning), it is likely that mTOR is driven to be constantly active revving up cancer growth.

"This could be a mechanism that allows the cancer to grow regardless of what the environment is telling it," Sardiello said. "We are excited that these findings open possible novel approaches to treat cancer. In our lab, we are trying to use this knowledge to find ways around neurodegenerative diseases."

What causes Alzheimer's disease? The answer could be right under our noses, says leading expert Professor Ruth Itzhaki. Her latest paper presents a lifetime of research evidence that the herpes virus responsible for cold sores can also cause Alzheimer's - and new data which show antiviral drugs drastically reduce risk of senile dementia in patients with severe herpes infections. The review in Frontiers in Ageing Neuroscience raises the tantalizing prospect of a simple, effective preventive treatment for one of humanity's costliest disorders.

The HSV1 theory of Alzheimer's disease

Herpes viruses are the dreaded 'gift that keeps on giving'. They remain lifelong in our neurons and immune cells, reactivating and resurfacing in characteristic blisters when we're run down by stress or illness. Most people are infected by Herpes Simplex Virus 1 (HSV1) by the time they reach old age.

But what happens to infected neurons in our brain during this reactivation?

"HSV1 could account for 50% or more of Alzheimer's disease cases," says Professor Itzhaki, who has spent over 25 years at the University of Manchester investigating a potential link.

HSV1 is better known as the cause of cold sores. Itzhaki has shown previously that cold sores occur more frequently in carriers of APOE-ε4 - a gene variant that confers increased risk of Alzheimer's.

"Our theory is that in APOE-ε4 carriers, reactivation is more frequent or more harmful in HSV1-infected brain cells, which as a result accumulate damage that culminates in development of Alzheimer's."

Proving the theory

Few countries collect the population data required to test this theory - for example, to find out whether antiviral treatments reduce dementia risk.

In Taiwan however, researchers have done just that. There, 99.9% of the population is enrolled in a National Health Insurance Research Database, which is being extensively mined for information on microbial infections and disease. In 2017-2018 three studies were published describing Taiwanese data on the development of senile dementia - of which Alzheimer's is the main cause - and the treatment of patients with marked overt signs of infection with HSV or varicella zoster virus (VZV, the chickenpox virus).

"The striking results include evidence that the risk of senile dementia is much greater in those who are infected with HSV, and that anti-herpes antiviral treatment causes a dramatic decrease in number of those subjects severely affected by HSV1 who later develop dementia."

Previous findings from Itzhaki's own research group provide a mechanistic link which supports these epidemiological findings. They found that HSV1 causes protein deposits characteristic of Alzheimer's: 'plaques' between neurons, and 'tangles' inside of them.

"Viral DNA is located very specifically within plaques in postmortem brain tissue from Alzheimer's sufferers. The main proteins of both plaques and tangles accumulate also in HSV1-infected cell cultures - and antiviral drugs can prevent this."

Towards a cure

"It should be stressed that the results of these Taiwanese studies apply only to severe HSV1 (or VZV) infections, which are rare," admits Itzhaki. "Ideally, we would study dementia rates amongst people who have suffered mild HSV1 infection, including herpes labialis (cold sores) or mild genital herpes, but these are far less likely to be documented."

Although further work is needed to confirm and define a causal link between HSV1 infection and Alzheimer's, Itzhaki is enthusiastic about the treatment prospects.

"Considering that over 150 publications strongly support an HSV1 role in Alzheimer's, these Taiwan findings greatly justify usage of antiherpes antivirals - which are safe and well-tolerated - to treat Alzheimer's disease.

"They also incentivize development of an HSV1 vaccine, which would likely be the most effective treatment."

This echoes the growing use worldwide of human papillomavirus (HPV) vaccination to prevent cervical cancer - another virus-disease link which emerged in a similar process of research.

According to a first-of-its-kind international study, a new definition of Pediatric Acute Respiratory Distress Syndrome (PARDS) results in a more accurate diagnosis of many more children with the rapidly progressive disease than the widely used adult definition.

Findings from the Pediatric ARDS Incidence and Epidemiology Study were published online on Oct. 18 by the leading medical journal, The Lancet Respiratory Medicine.

"PARDS is a major source of illness and death in critically ill patients, yet the disease historically has been underdiagnosed in children," said lead author Robinder G. Khemani, MD, MsCI, associate director of research for the Department of Anesthesiology and Critical Care Medicine at Children's Hospital Los Angeles.

The study represents the largest-ever international cohort of children with PARDS. A total of 700 patients were studied in 145 pediatric intensive care units (PICU) in 27 countries.

Acute respiratory distress syndrome causes fluid to leak into the lungs, making it very difficult to breathe and leading to low oxygen in the blood, called hypoxemia. Pediatric intensivists have long recognized that the condition manifests differently in children than in adults. However, until recently, there was no pediatric-specific diagnostic criteria.

In 2015, the Pediatric Acute Lung Injury Consensus Conference (PALICC) issued a definition to overcome limitations of existing adult definitions, such as the widely accepted Berlin Definition. "Prior to the PALICC standard, pediatricians had been using adult definitions and applying them to children," said Khemani, who headed the PALICC definition subgroup.

Since then, a handful of single-center or regional studies have supported the PALICC definition but its performance in a large international sample was unknown until now. Working from May 2016 to June 2017, the investigators found that of the 708 pediatric patients who met PALICC criteria, only 32% also met the adult definition, meaning that two-thirds of the children would not have been accurately diagnosed.

In one major difference between the two definitions, pediatric guidelines recommend the use of pulse oximetry, a noninvasive method for monitoring a patient's oxygen saturation, while the adult guidelines call for usage of an invasive arterial blood gas test.

In a key finding, the investigators discovered that, contrary to previous thinking, mild and moderate PARDS have similar mortality rates, between 10 and 15%. However, patients with severe PARDS experience a huge jump in mortality -- to 30%.

Another finding concluded that over 3% of all PICU patients and 6% of patients placed on a ventilator develop PARDS. Internationally, PARDS carries a high mortality rate for children--more than 17% overall.

"The study conclusively shows that the PALICC definition can be used as a framework for future research, to inform clinical decisions and to test new treatment strategies," said Khemani, associate professor of clinical pediatrics at the Keck School of Medicine of the University of Southern California

In the future, the investigators plan to release the data for open access, to inspire other studies.

Among several forms of pancreatic cancer, one of them affects specifically women, often young. How is this possible, even though the pancreas is an organ with little exposure to sex hormones? This pancreatic cancer, known as "mucinous cyst", has strange similarities with another mucinous cancer, affecting the ovaries. By conducting large-scale analyses of genomic data, researchers at the University of Geneva (UNIGE) and at the University Hospitals of Geneva (HUG), Switzerland, in collaboration with colleagues from the United States have provided an answer: both tumours originate from embryonic germ cells. While still undifferentiated, these cells migrate to the reproductive organs. On their way, some can mistakenly stop in other organs, bringing a risk of tumour that may occur 30 years later. By allowing a better classification of these mucinous tumours, this study, to be read in the Journal of Pathology, paves the way for a more appropriate and personalized management aligned with the tumour's origin.

Mucinous tumours of the ovary and pancreas affect young women - between 30 and 40 years of age. They take the form of a large cyst, a kind of ball filled with liquid. Rare - they account for about 3% of ovarian and pancreatic cancers - they are usually treated by surgery. Taken in time, the cancerous cyst is completely removed. However, in 15% of cases, the cyst breaks before surgery; the cancer cells spread into the peritoneum, giving rise to metastases that are highly resistant to chemotherapy. In such cases, the survival prognosis of patients does not exceed one year.

"Initially, this work was based on clinical observation," says study leader Dr. Intidhar Labidi-Galy, a researcher at the Translational Research Centre in Onco-haematology at the UNIGE Faculty of Medicine and a physician at the HUG. "As a specialist in ovarian cancer, I came across an article detailing the genetic profile of mucinous tumours of the pancreas. To my great surprise, they had the same genetic alterations as mucinous tumours of the ovary, although these two organs have no direct relationship with each other. Dr. Kevin Elias, assistant professor of obstetrics and gynecology at Brigham's and Women's Hospital, Boston, USA and first author of the paper, identifies the close links between the two tumours: "We found the same genetic mutations, the same types of victims - young women, often smokers - and, even more surprisingly, ovarian tissue in pancreatic cysts."

A common origin

Why is a non-gynaecological cancer almost exclusively female? What is the link between the ovary and the pancreas? "It is only during embryogenesis that these organs are really close. At the very beginning of pregnancy, the embryo possesses primordial germ cells - in a way, precursors of gametes, oocytes or spermatozoa - which, between 4 and 6 weeks of pregnancy, makes a long migration in the human body. They pass behind the future pancreas and arrive in the outline of the gonads, around the 7th week of pregnancy. Most likely, some of these germ cells stop on the way," says Dr. Labidi-Galy.

Using public databases, Kevin Elias and Petros Tsantoulis from UNIGE, together with Intidhar Labidi-Galy and co-leader Ronny Drapkin from University of Pennsylvania have developed a transcriptomic profile - which identifies gene expression levels in a tissue - of primordial germ cells at 6, 7, 11, 16 and 17 weeks of pregnancy, as well as of tumoral and healthy ovarian and pancreatic cells.

The researchers then compared these data, on one hand with the pancreas and on the other hand with the ovary, by studying for each of these two organs the profile of healthy tissues, mucinous tumours and other types of tumours. Their results are clear: in both cases, the transcriptomic profile of the mucinous tumour is far away from the supposed tissue of origin (ovary or pancreas), but very close to the primordial germ cells. This proves that these tumours are closer to the primordial germ cells than to the organ in which they developed.

Unexpected stops during migration

These results indicate that a stop in cell migration that occurred accidentally during the embryonic life of these women may, decades later, be expressed as cancer, depending on their other risk factors (e.g. smoking) and where in the body these primordial germ cells have settled. Indeed, while the scientists have examined the pancreas and ovary, similar cases have been reported everywhere on the migration line of germ cells, particularly in the liver or peritoneum.

"Our results will not change the surgical management of these patients, but may lead us to reflect on chemotherapy protocols. These rare tumours are a bit like the orphan diseases of cancers, for which there are no standard treatments. By linking them to other cancers, we hope to identify treatments that would be effective. For each mutation, what is the best treatment? We are here at the heart of personalized oncology: knowing your enemy in every detail makes it easier to fight him," concludes Dr. Labidi-Galy.